C. M. Yip
B.A.Sc. (Toronto), Ph.D. (Minnesota), P.Eng.Donnelly CCBR, 160 College Street, Room 404
Tel.: 416-978-7853
Email: christopher.yip@utoronto.ca
Web site: http://bigten.med.utoronto.ca
Awards
Molecular Imaging Corp. Young Biological Scanning Probe Microscopist of the Year, 1998
Premier’s Research Excellence Award, 1999
Faculty Teaching Award, 2000/01
Graduate Faculty Teaching Award for Sustained Contribution to Excellence in Graduate Teaching, University of Toronto Faculty of Medicine, 2008
Fellow, American Association for the Advancement of Science, 2009
Memberships
Microscopical Soc. of Canada - Ont. Section Chair
Professional Engineers of Ontario
American Chemical Society
Chemical Institute of Canada
Canadian Society for Chemical Engineering
Biophysical Society
Research Interests
Molecular Engineering and Single Molecule Biophysics
Molecular engineering refers to the molecular level control of materials through rational control of chemical structure, molecular conformation, and solid-state packing. The study of molecular engineering draws influences from fields as diverse as organic chemistry, biochemistry, structural biology, and chemical engineering. Indeed control over processes ranging from the crystallization of biomolecules and pharmaceuticals to the formation of protein complexes requires an in-depth understanding of the subtle structural and chemical factors controlling the processes of molecular self-assembly and recognition.
Our research efforts are directed at the in situ characterization of molecular self-assembly, which has clear implications for understanding processes ranging from the crystallization of biomolecules and pharmaceuticals to the interaction of protein and drug molecules with cellular membranes. Through a combination of in situ scanning probe microscopy (SPM) with other techniques including circular dichroism, light scattering, X-ray scattering, NMR spectroscopy, and infrared and Raman spectroscopy, we are endeavouring to develop models for these processes. Collaborations with structural biology and crystallography research groups at the University of Toronto in additional to external programs with pharmaceutical companies offer an excellent opportunity to study a variety of biomolecular phenomena and processes of therapeutic interest.
The design of novel molecules and proteins for therapeutic applications requires an understanding of how these molecules interface with their complementary sites in the body. Thus it becomes clearly important to characterize the structure of these binding sites and X-ray crystallography remains one of the main means for acquiring high-resolution structural data. However, traditional diffraction techniques cannot readily provide information about the kinetics of crystal growth or local disorder.Thus we are using in situ SPM to assess the structure of protein crystals at the crystal-solution interface. These studies will provide information on the kinetics of crystal growth and, perhaps more importantly, the role of defects on crystal dissolution, which is of key importance for the bioavailability of crystalline pharmaceuticals. We are also investigating the formation of protein complexes on model lipid bilayers. This approach has shown promise for understanding the mechanisms associated with protein complexation on cell membranes, including the action of viral proteins. Similarly, we are also studying the process of protein aggregation and fibril formation at model interfaces, which has significant implications for the design of novel biomimetic materials. The ability to achieve near-molecular scale resolution in the absence of staining and high vacuum techniques suggests an ideal opportunity to characterize the factors that influence these processes under native conditions.
The high force sensitivity of the scanning probe microscope has enabled researchers to directly measure intermolecular forces, including ligand-receptor interactions, using chemically modified SPM tips and surface immobilized molecules. This approach affords a unique opportunity to directly probe an envelope of association energies, which complements traditional equilibrium association measurements and has clear application to the characterization of other systems including force mapping of biological membrane surfaces and the interaction between novel ligands and specific binding sites which may have importance for the screening of new drug molecules.
Furthermore, our group is actively involved in the design, fabrication, and application of novel molecular scale functional imaging tools as well as computational approaches to understanding molecular structure, function, and assembly.
Selected Publications
Tracking Molecular Interactions in Membranes By Simultaneous ATR-Fourier-Transform Infrared Spectroscopy- Atomic Force Microscopy.
Verity, J., Chhabra, N., Sinnathamby, K., Yip, C.M. MS ID # BIOPHYSJ/
2009/156133 In press
Color From Colorless Nanomaterials: Bragg Reflectors Made Of Nanoparticles Puzzo, D.P.; Bonifacio, L.D.; Oreopoulos, J.; Yip, C.M.; Manners, I.; Ozin, G.A. J. Materials Chemistry, 2009, In press.
10.1039/b903229
Probing Membrane Order and Topography in Supported Lipid Bilayers by Combined Polarized Total Internal Reflection Fluorescence
- Atomic Force Microscopy Oreopoulos, J., Yip, C.M. Biophysical J.
2009, 96, 1970-1984
Variations in Mass Transfer to Single Endothelial Cells, Van Doormal, M.A., Zhang, J., Wada, S., Shaw, J.E., Won, D., Cybulsky, M.I., Yip, C.M., Ethier, C.R., Biomechanics and Modeling in Mechanobiology, 2009;8(3):183-193
Biodegradable Quantum Dot Nanocomposites for Live Cell Cytosolic Delivery and Subcellular Imaging. Kim, B.Y.S., Jiang, W., Oreopoulos, J., Yip, C.M., Rutka, J.T., Chan, W.C.W. NanoLetters
2008 , 8(11), 3887-92
Lsr2 of Mycobacterium Tuberculosis is a DNA-Bridging Protein.
Chan, J.M., Ren, H., Shaw, J.E., Wang, Y.J., Li, M., Kocincova, D., Yip, C.M., Reyat, J-M., Liu J. Nucleic Acids Research 2008, 36 (7)
2123-2135
Molecular Chaperone Hsp90 Stabilizes Pih1/Nop17 to Maintain R2TP Complex Activity That Regulates snoRNA Accumulation. Zhao, R., Kakihara, Y., Gribun, A., Huen, J., Yang, G., Khanna, M., Constanza, M., Brost, R.L., Boone, C., Hughes, T.R., Yip, C.M., Houry, W.A., J.
Cell Biology 2008, 108(3): 563-578
Cationic Peptide-Induced Remodelling Of Model Membranes: Direct Visualization By In Situ Atomic Force Microscopy Shaw, J.E., Epand, R.F, Hsu, J.C.Y., Epand, R.M. Yip, C.M. J. Structural Biology 2008,
162(1):121-138
Molecular Imaging of Membrane Interfaces Reveals Mode of β- Glucosidase Activation by Saposin C. Alattia, J.R., Shaw, J.E., Yip, C.M., Prive, G.G. Proc. Natl. Acad. Sci. USA, 2007, 104 (44),
17394-17399
Molecular Dynamics Simulations of Indolicidin Association with Model Lipid Bilayers. Hsu, J., Yip, C.M. Biophysical Journal Letters
2007 92(12):L100-2 (100% effort)
In Situ Scanning Probe Microscopy Studies of Tetanus Toxin- Membrane Interactions. Slade, A.L; Schoeniger, J.S.; Sasaki, D.Y.; Yip, C.M Biophysical Journal 2006 91(12), 4565-4574
Direct Visualization of Saposin Remodelling of Lipid Bilayers Alattia, J-R., Shaw, J.E., Yip, C.M., Prive, G.G. J.Mol. Biol. 2006, 362(5), 943-953
Tracking Peptide–Membrane Interactions: Insights From In Situ Coupled Confocal – Atomic Force Microscopy Imaging Of NAP-22 Peptide Insertion And Assembly Shaw, J.E., Epand, R.E., Sinnathamby, K.; Li, Z., Bittman, R., Epand, R.M., Yip, C.M. J. Struct. Biol. 2006, 155(3):
458-469
Amyloid Fibrils of Glucagon Characterized by High-Resolution Atomic Force Microscopy De Jong, K.L., Incledon, B., Yip, C.M., DeFelippis, M.R. Biophysical Journal 2006 Sep;91(5):1905-191
Force-Induced Insulin Dimer Dissociation: A Molecular Dynamics Study Kim, T., Rhee, A., Yip, C.M. JACS. 2006, 128(16):5330-5331
Correlated Fluorescence-AFM Microscopy of Membrane Domains: Nature of Fluorescence Probes Determines Localization of Lipids Shaw, J.E., Epand, R.F., Epand, R.M.; Li. Z.; Bittman, R.; Yip, C.M.
Biophysical J 2006 90(6):2170-2178
Mechanisms of Antimicrobial Peptide Action: Studies of Indolicidin Assembly at Model Membrane Interfaces by In Situ Atomic Force Microscopy. Shaw, J.E.; Alattia, J.-R., Verity, J.E.; Prive, G.G., Yip, C.M. J. Struct. Biol. 2006, 154(1):42-58
Cholesterol-Dependent Partitioning of PI(4,5)P2 into Membrane Domains by the Amino Terminal Fragment of NAP-22 Epand, R.M.; Vuong, P.; Yip, C.M.; Epand, R.F. Biochem. J 2004, 379(3), 527-532